| BackgroundBilirubin is the waste of red blood cells after the metabolism of hemoglobin,and hyperbilirubinemia is a common clinical symptom of premature children.At present,a consensus has been formed that bilirubin accumulated in premature infants with hyperbilirubinemia which will cause significant damage to the central nervous system;on the other hand,hyperbilirubinemia also cause various damage in kidney function of premature infants.Urinary cystatin C(Cys C),urinary renal injury molecule 1(KIM-1),and urinary neutrophil gelatinase-related lipid transport protein(NGAL)are good indicators reflecting renal function damage,but the effects of hyperbilirubinemia on renal function in preterm infants were rarely reported.It is well known that the use of renal puncture in children combined renal biopsy is the golden standard of the severity of kidney damage,but in the prenatal habitus is generally weaker,and the tolerance of the invasive operation is much lower than ordinary children.Therefore,many premature children are not suitable for renal puncture operation.Besides,hardly parents of preterm children agreed to let the premature children receive kidney puncture.A clear,quantifiable judgment of hyperbilirubinemia leading to the degree of renal injury in preterm infants is very difficult to achieve on clinic.Therefore,how to determine early kidney injury by hyperbilirubinemia of premature infants has become a difficult task in clinical practice.In this study,urine urinary Cys C,urinary KIM-1,urinary NGAL,blood urea nitrogen(BUN)and serum creatinine(Cr)were measured to evaluate the diagnostic significance of renal function by hyperbilirubinemia in premature infants.ObjectiveUrinary Cys C,urinary KIM-1,urine NGAL,BUN and Cr levels were measure toinvestigate the changes of urinary NGAL,urinary Cys C and urinary KIM-1 in hyperbilirubinemia of premature infants.And to provide scientific basis for the prognosis and treatment of renal dysfunction in premature infants with hyperbilirubinemia.MethodsA total of 115 patients with neonatal bilirubinemia were enrolled who were hospitaled in Zhengzhou children’s hospital internal medicine departemnt from December 2011 to December 2015.All premature infants were excluded from infection,sepsis,drug effects,intrauterine distress and other serious complications.30 cases of non-hyperbilirubinemia premature infants were selected as the control group.All premature children were not found any the primary disease with kidney damage existing.There was no statistically significant difference in gestational age,age,sex,and birth weight of preterm infants in two groups.According to the serum total bilirubin(TBIL)levels,the premature infants were divided into severe group,moderate group,mild group and control group.10 m L of morning clean urine were collected for all subjects on the 2ndday after hospitalized,and the urine specimens were placed in the test tube to centrifuge at 2500 rpm / min for 20 min.Then the urine sample supernatant were collected in the EP tube.All specimens were placed in-80 ℃ ultra-low temperature refrigerator,and all the process strictly followed the laboratory procedures to avoid repeated freezing and thawing affect the test results.Urinary Cys C,urinary KIM-1 and urinary NGAL were detected by enzyme-linked immunosorbent assay(ELISA),and comprehensive analysis was performed.2mL of venous blood was drawn for every infant and analyzed by Hitachi 7600-110 automatic biochemical analysis detector.The serum levels of TBIL were measured by continuous monitoring of 2,4-dichloroaniline diazo method,and the concentration of Cr was determined by enzymatic continuous monitoring method.The level of BUN was measured by continuous monitoring of urease.Multiple-group comparisons were performed using one-way ANOVA,and the LSD method was used for comparison between two groups.Correlation analysis was completed by using bivariate Pearson linear correlation analysis.The diagnostic significance of each index was evaluated by the receiver operating characteristic(ROC)curve.ResultsThere were significant differences in urine CysC,urinary KIM-1 and urinary NGAL between the severe group and the control group,the moderate group and the control group(P<0.01).There was no significant difference in urine Cys C,urinary KIM-1 and urinary NGAL between the mild group and the control group(P >0.05).There was significant difference in urinary Cys C,urinary KIM-1 and urinary NGAL between mild group and severe group,severe group and moderate group,moderate group and mild group(P<0.01).There was no significant difference in BUN between the any two groups(P>0.05)but the difference of Cr was statistically significant(P <0.05).Urine NGAL,urine CysC,urine KIM-1 were positively correlated with TBIL(r = 0.649,0.869,0.744,all P<0.01);BUN,Cr and TBIL had no correlation(r = 0.098,-0.010,all P>0.05).Urinary NGAL,urinary CysC,urinary KIM-1,BUN and Cr were not correlated(all P>0.05).Urine NGAL,urine CysC and urine KIM-1 were positively correlated(r=0.692,0.517,0.785,all P<0.01).ROC curve analysis showed that the sensibility and specificity of urinary NGAL levels were significantly higher in the diagnosis of neonatal renal injury of premature infants with hyperbilirubinemia,and the area under the curve(AUC)was 0.980(P < 0.05).The sensitivity and specificity of urinary NGAL level were 94.6% and 90% respectively when the cutoff was 3.91 m g/L.The sensitivity and specificity of urinary CysC level in the diagnosis of renal injury in premature infants with hyperbilirubinemia were also higher,and AUC was 0.996(P<0.05).When cutoff of urinary CysC level was 0.063 mg/ L,the sensitivity and specificity were 93.0% and 98.5%,respectively.The sensitivity and specificity of urinary KIM-1 levels in the diagnosis of renal injury in preterm infants with hyperbilirubinemia were normal with AUC value of 0.859(P<0.05).The sensitivity and specificity were 78.3% and 82.1% respectively when the cutoff of KIM-1 level in urine was 3.28 pg/mL.The AUC value of BUN,Cr AUC were lower,for 0.5-0.7,and the diagnosis effect was poor.Conclusions1.Hyperbilirubinemia can lead to renal function damage in preterm infants,and the higher the level of serum TBIL,the more severe kidney damage caused.2.BUN and blood Cr are not suitable as the indicator to reflect renal injury caused byhyperbilirubinemia in premature infants.3.The sensitivity of urine Cys C,urinary KIM-1 and urine NGAL were significantly higher than BUN and blood Cr.When the cutoff of urinary NGAL level was 3.91 μg/ L and urinary CysC level was 0.063 mg /L,the sensitivity and specificity were high.When the cutoff of urinary KIM-1 level was 3.28 pg/mL,its sensitivity and specificity was general.The diagnostic value of urinary NGAL and urinary Cys C were higher than urinary KIM-1. |
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